Abstract
Hospitalization costs on human metapneumovirus (hMPV) are needed to inform healthcare priorities, including vaccine and treatment development. Among 5775 adult hospitalizations with hMPV or respiratory syncytial virus (RSV), hMPV was associated with shorter length of stay but greater frequency of pneumonia, resulting in adjusted mean costs comparable to RSV hospitalization.
Keywords: adult, cost, hospitalization, human metapneumovirus, respiratory syncytial virus
Acute respiratory infections caused by human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) often present similarly and can significantly impact morbidity and mortality, especially in vulnerable adult and pediatric populations. Awareness of these pathogens as important causes of severe disease in high-risk and older adults may be low particularly for hMPV [1]. Although the economic impact of influenza-, SARS-CoV-2-, and RSV-associated disease in adults has been studied extensively, there are limited data on hMPV-associated healthcare costs in adult populations. A current estimate of the cost of hospitalization of adults with hMPV or RSV may increase awareness of the impact of hMPV- and RSV-associated disease in this understudied population. Furthermore, estimating the cost of hospitalization of adults with hMPV is important to the economic analysis of vaccines and treatments for hMPV currently under development prior to their introduction. Therefore, we evaluated and compared costs for a cohort of adults ≥18 years of age.
METHODS
Setting
This retrospective cohort study was conducted at Kaiser Permanente Southern California (KPSC), an integrated system providing healthcare at 16 large, community-based hospitals and associated clinics for >4.8 million members whose demographics closely mirrors that of the Southern California population in the United States [2]. Kaiser Permanente Southern California electronic health records include sociodemographics, healthcare utilization, diagnoses, laboratory tests, procedures, pharmacy utilization, vaccinations, and membership history.
Study Cohort
The study cohort consisted of hospitalized adults ≥18 years of age who tested positive for hMPV or RSV by reverse transcription-polymerase chain reaction (RT-PCR) between 7 days prior to 2 days following admission between 01 July 2011 and 30 June 2024 from KPSC. Hospitalizations with <1 year of continuous KPSC membership before admission or missing diagnosis-related group (DRG) codes were excluded from analysis.
The analysis included the first hMPV or RSV test-positive hospitalization per season (1 July to 30 June) and repeat hospitalizations for the same individual in separate seasons were included. The unit of analysis was hospitalization. The KPSC Institutional Review Board approved this study and waived the requirement for informed consent.
Outcome
The primary outcome of the study was total hospitalization costs. Each hospitalization record included a DRG code based on principal and secondary diagnoses and procedures. Using a utilization-based cost algorithm [3], we assigned nationally recognized direct healthcare costs to each hospitalization record. Daily average cost per DRG was derived from patients ≥18 years of age using the 2020 National Inpatient Sample (NIS) [4]. Total hospitalization costs were calculated by multiplying mean daily cost per DRG derived from the 2020 NIS by length of stay (LOS) for each hospital record. To compare costs across published studies and our findings, we applied the consumer price index for medical care services to report costs in 2020 US dollars (USD).
Statistical Analysis
We described patient sociodemographic and clinical characteristics at hospital admission. Clinically relevant variables including age, sex, race/ethnicity, baseline healthcare utilization, immunocompromised status, Charlson comorbidity score, and year and month of hospital admission were included as covariates in adjusted models. Absolute standardized differences (ASDs) between hMPV and RSV hospitalizations were calculated; variables with ASD >0.1 were included as additional covariates. t-tests and χ2 tests were used to compare mean LOS, occurrence of complications during the hospital stay, and proportion of DRG codes in hMPV and RSV hospitalizations.
Generalized linear regression models (GLMs) with a gamma distribution and log link were used to estimate the population mean cost with 95% confidence intervals (CIs) for hMPV and RSV hospitalizations. Differences in mean cost with 95% CI between hMPV and RSV hospitalizations were estimated using GLMs. Model-based contrasts were reported for both unadjusted and adjusted cost estimates. Stratified analyses were conducted based on sex (male, female), age at hospital admission (18–49, 50–59, 60–74, and ≥75 years), and pre- and postappearance of COVID-19. Sensitivity analyses were conducted by including hospitalizations with missing DRGs. Costs for missing DRG records were imputed using predicted values from a GLM applied to the entire sample. Additional sensitivity analyses were conducted by selecting appropriate families and link functions based on the modified Park, Pregibon link, Pearson correlation, and modified Hosmer and Lemeshow tests [5] and by accounting for within-person correlation in repeated hospitalizations.
All statistical analyses were performed using SAS 9.4 (SAS Institute) or Stata 18 (StataCorp LLC). P < .05 was considered statistically significant.
RESULTS
We included 5775 hospitalizations among 5650 adults who tested positive for hMPV (n = 2810 hospitalizations) or RSV (n = 2965 hospitalizations) in this analysis. Compared with patients with RSV, those with hMPV were younger and had lower proportions with kidney disease, Charlson comorbidity score ≥2, or immunocompromising conditions. Admissions associated with hMPV occurred more frequently between January and June, while RSV admissions were more common between October and March (ASD >0.1; Table 1).
Table 1.
Baseline Patient Characteristics Associated With Hospitalization for hMPV and RSV
| hMPV Hospitalizations N = 2810a |
RSV Hospitalizations N = 2965b |
ASD | |
|---|---|---|---|
| Age on date of admission, year | … | … | 0.103 |
| Mean (SD) | 71.0 (16.1) | 72.6 (15.4) | … |
| Median (Q1, Q3) | 74 (62.0, 83.0) | 75 (64.0, 84.0) | … |
| Age on date of admission, year, n (%) | … | … | 0.105 |
| 18–49 | 299 (10.6) | 244 (8.2) | … |
| 50–59 | 307 (10.9) | 286 (9.6) | … |
| 60–74 | 861 (30.6) | 900 (30.4) | … |
| &ge75 | 1343 (47.8) | 1535 (51.8) | … |
| Sex, n (%) | … | … | 0.032 |
| Female | 1673 (59.5) | 1718 (57.9) | … |
| Male | 1137 (40.5) | 1247 (42.1) | … |
| Race/ethnicity, n (%) | … | … | 0.064 |
| Non-Hispanic White | 1295 (46.1) | 1343 (45.3) | … |
| Non-Hispanic Black | 309 (11.0) | 374 (12.6) | … |
| Hispanic | 843 (30.0) | 906 (30.6) | … |
| Non-Hispanic Asian | 315 (11.2) | 296 (10.0) | … |
| Other/multiple/unknown | 48 (1.7) | 46 (1.6) | … |
| Length of continuous membership,c year, n (%) | … | … | 0.067 |
| 1–5 | 543 (19.3) | 522 (17.6) | … |
| 6–10 | 435 (15.5) | 416 (14.0) | … |
| ≥11 | 1832 (65.2) | 2027 (68.4) | … |
| Number of prior outpatient and virtual visits,d n (%) | … | 0.054 | … |
| 0 | 50 (1.8) | 42 (1.4) | … |
| 1–4 | 338 (12.0) | 346 (11.7) | … |
| 5–10 | 705 (25.1) | 696 (23.5) | … |
| ≥11 | 1717 (61.1) | 1881 (63.4) | … |
| Number of prior emergency department visits,d n (%) | … | 0.055 | … |
| 0 | 1146 (40.8) | 1134 (38.2) | … |
| 1 | 692 (24.6) | 742 (25.0) | … |
| ≥2 | 972 (34.6) | 1089 (36.7) | … |
| Number of prior hospitalizations,d n (%) | … | … | 0.096 |
| 0 | 1788 (63.6) | 1761 (59.4) | … |
| 1 | 535 (19.0) | 591 (19.9) | … |
| ≥2 | 487 (17.3) | 613 (20.7) | … |
| Vaccination,d n (%) | … | … | … |
| Influenza vaccine | 1946 (69.3) | 2063 (69.6) | 0.007 |
| COVID-19 vaccine | 401 (14.3) | 384 (13.0) | 0.039 |
| RSV vaccine | 28 (1.0) | 6 (0.2) | 0.103 |
| Chronic diseases,d n (%) | … | … | … |
| Kidney disease | 1116 (39.7) | 1327 (44.8) | 0.102 |
| Heart disease | 1079 (38.4) | 1194 (40.3) | 0.038 |
| Lung disease | 1374 (48.9) | 1506 (50.8) | 0.038 |
| Liver disease | 260 (9.3) | 278 (9.4) | 0.004 |
| Diabetes | 1298 (46.2) | 1407 (47.5) | 0.025 |
| Immunocompromised on date of admission, n (%) | 536 (19.1) | 688 (23.2) | 0.101 |
| Charlson comorbidity scored,e | … | … | 0.069 |
| Mean (SD) | 4.5 (2.6) | 4.7 (2.7) | … |
| Median (Q1, Q3) | 4 (2.0, 6.0) | 4 (2.0, 6.0) | … |
| Charlson comorbidity score,d,e n (%) | … | … | 0.132 |
| 0 | 261 (9.3) | 191 (6.4) | … |
| 1 | 342 (12.2) | 299 (10.1) | … |
| ≥2 | 2207 (78.5) | 2475 (83.5) | … |
| Frailty indexd,f | … | … | 0.074 |
| Mean (SD) | 0.19 (0.06) | 0.19 (0.06) | … |
| Median (Q1, Q3) | 0.18 (0.15, 0.22) | 0.19 (0.15, 0.23) | … |
| Frailty index,d,f n (%) | … | … | 0.073 |
| Q1 (0.15), least frail | 746 (26.5) | 700 (23.6) | … |
| Q2 (0.18) | 700 (24.9) | 745 (25.1) | … |
| Q3 (0.23) | 691 (24.6) | 750 (25.3) | … |
| Q4 (0.43), most frail | 673 (24.0) | 770 (26.0) | … |
| Body mass index,g kg/m2, n (%) | … | … | 0.079 |
| <18.5 | 112 (4.0) | 125 (4.2) | … |
| 18.5 to <25 | 739 (26.3) | 827 (27.9) | … |
| 25 to <30 | 752 (26.8) | 848 (28.6) | … |
| 30 to <40 | 840 (29.9) | 832 (28.1) | … |
| ≥40 | 342 (12.2) | 310 (10.5) | … |
| Unknown | 25 (0.9) | 23 (0.8) | … |
| Smoking,g n (%) | … | … | 0.066 |
| Never | 1692 (60.2) | 1690 (57.0) | … |
| Ever | 1096 (39.0) | 1252 (42.2) | … |
| Unknown | 22 (0.8) | 23 (0.8) | … |
| Medicaid, n (%) | 372 (13.2) | 371 (12.5) | 0.022 |
| Neighborhood median household income, n (%) | … | … | 0.043 |
| <$40 000 | 258 (9.2) | 301 (10.2) | … |
| $40 000–$59 999 | 714 (25.4) | 728 (24.6) | … |
| $60 000–$79 999 | 675 (24.0) | 736 (24.8) | … |
| ≥$80 000 | 1160 (41.3) | 1196 (40.3) | … |
| Unknown | 3 (0.1) | 4 (0.1) | … |
| ARI/LRTD on date of admission, n (%) | 2709 (96.4) | 2837 (95.7) | 0.037 |
| Year of seasons (July to June), n (%) | … | … | 0.454 |
| 2011–2012 | 55 (2.0) | 23 (0.8) | … |
| 2012–2013 | 27 (1.0) | 135 (4.6) | … |
| 2013–2014 | 244 (8.7) | 122 (4.1) | … |
| 2014–2015 | 150 (5.3) | 312 (10.5) | … |
| 2015–2016 | 404 (14.4) | 315 (10.6) | … |
| 2016–2017 | 277 (9.9) | 460 (15.5) | … |
| 2017–2018 | 351 (12.5) | 386 (13.0) | … |
| 2018–2019 | 346 (12.3) | 256 (8.6) | … |
| 2019–2020 | 171 (6.1) | 200 (6.7) | … |
| 2020–2021 | 0 (0.0) | 4 (0.1) | … |
| 2021–2022 | 75 (2.7) | 84 (2.8) | … |
| 2022–2023 | 371 (13.2) | 263 (8.9) | … |
| 2023–2024 | 339 (12.1) | 405 (13.7) | … |
| Month of hospital admission, n (%) | … | … | 0.757 |
| July to September | 96 (3.4) | 33 (1.1) | … |
| October to December | 264 (9.4) | 752 (25.4) | … |
| January to March | 1657 (59.0) | 2026 (68.3) | … |
| April to June | 793 (28.2) | 154 (5.2) | … |
| Coinfection,h n (%) | … | … | … |
| Adenovirus | 7 (0.2) | 8 (0.3) | 0.004 |
| Coronavirus (229E, HKU1, NL63, OC43) | 28 (1.0) | 37 (1.2) | 0.024 |
| SARS-CoV-2 | 5 (0.2) | 9 (0.3) | 0.026 |
| hMPV | NA | 11 (0.4) | NA |
| Human rhinovirus/enterovirus | 48 (1.7) | 79 (2.7) | 0.065 |
| Influenza | 16 (0.6) | 44 (1.5) | 0.091 |
| Parainfluenza | 8 (0.3) | 9 (0.3) | 0.004 |
| RSV | 11 (0.4) | NA | NA |
| Chlamydia pneumoniae | 0 | 0 | NA |
| Mycoplasma pneumoniae | 0 | 0 | NA |
Abbreviations: ARI, acute respiratory infection; ASD, absolute standardized difference; hMPV, human metapneumovirus; LRTD, lower respiratory tract disease; n, number; NA, not applicable; Q, quartile; RSV, respiratory syncytial virus; SD, standard deviation.
aRepresenting 2800 individuals.
bRepresenting 2949 individuals.
cDefined based on all available medical records prior to the hospital admission date.
dDefined in the 1 year prior to the hospital admission date.
ePossible range: 0–29. A weighted score of major comorbidities, assigning higher weights to severe conditions, which predicts mortality. Quan H, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. American Journal of Epidemiology 173.6 (2011): 676–682.
fPossible range: 0–1. A validated claims-based frailty index which predicts disability, falls, and skilled nursing facility use. Kim DH, et al. Measuring frailty in Medicare data: development and validation of a claims-based frailty index. The Journals of Gerontology: Series A 73.7 (2018): 980–987.
gDefined as most recent assessment in 2 years prior to and including the hospital admission date.
hLimited to respiratory pathogen panel tests, descriptive only; some pathogen results may not be available for the entire study period.
The most frequent DRG codes were septicemia with multiple chronic conditions (∼30%) and pneumonia with multiple chronic conditions (∼10%) in both groups (Supplementary Table 1). Hospitalization with hMPV had slightly shorter mean LOS (6.4 vs 6.8 days, P = .018) but similar proportions with intensive care unit (ICU) admission (14.8% vs 16.5%, P = .084) and respiratory support requirement (24.8% vs 25.7%, P = .434) and a greater proportion with pneumonia (66.7% vs 56.8%, P <.001) when compared with hospitalization with RSV (Supplementary Table 2).
Adjusted mean hospitalization costs were $20 188 (95% CI: $19 317, $21 060) for hMPV and $21 759 (95% CI: $20 847, $22 670) for RSV, with a difference of −$1066 (95% CI: −$2413, $281; Table 2). Adjusted mean differences stratified by sex, age, and time period relative to the COVID-19 pandemic ranged from −$2371 (95% CI: −$6739, $1996) to $1521 (95% CI: −$2606, $5647). Sensitivity analysis including hospitalizations with missing DRG codes, as well as using alternative families and link functions and accounting for within-person correlation, showed consistent results (Supplementary Table 3).
Table 2.
Comparison of Crude and Adjusted Costs in 2020 US Dollars Between hMPV and RSV Hospitalizations
| HMPV Hospitalizations | RSV Hospitalizations | Difference In Mean Cost (hMPV−RSV) (95% CI) | ||||||
|---|---|---|---|---|---|---|---|---|
| Outcome | N | Crude Mean Cost (SD) | Adjusted Mean Costa (95% CI) | N | Crude Mean Cost (SD) | Adjusted Mean Costa (95% CI) | Unadjustedb | Adjusteda,c |
| Overall | 2810 | 20 102 (22 011) |
20 188 (19 317, 21 060) |
2965 | 21 852 (29 816) |
21 759 (20 847, 22 670) |
–1753 (–3101, –405) |
–1066 (–2413, 281) |
| Sex | ||||||||
| Male | 1137 | 20 232 (21 064) |
20 493 (19 079, 21 907) |
1247 | 21 772 (29 468) |
21 425 (20 024, 22 826) |
–1540 (–3633, 553) |
–936 (–2955, 1084) |
| Female | 1673 | 20 014 (22 637) |
20 407 (19 234, 21 580) |
1718 | 21 910 (30 075) |
21 565 (20 357, 22 772) |
–1896 (–3648, –144) |
–1155 (–2862, 552) |
| Age on date of admission, y | ||||||||
| 18–49 | 299 | 20 911 (25 702) |
21 968 (18 985, 24 951) |
244 | 21 313 (25 797) |
20 431 (17 389, 23 473) |
–401 (–4716, 3914) |
1521 (–2606, 5647) |
| 50–59 | 307 | 21 793 (26 266) |
21 763 (18 918, 24 608) |
286 | 24 996 (51 095) |
24 101 (20 838, 27 364) |
–3203 (–7775, 1369) |
–2371 (–6739, 1996) |
| 60–74 | 861 | 20 127 (21 325) |
20 457 (18 852, 22 063) |
900 | 23 345 (34 083) |
22 662 (20 932, 24 392) |
–3218 (–5674, –763) |
–2221 (–4618, 176) |
| ≥75 | 1343 | 19 520 (20 432) |
19 826 (18 545, 21 107) |
1535 | 20 476 (21 010) |
20 465 (19 244, 21 687) |
–957 (–2723, 810) |
–636 (–2398, 1125) |
| Periodsd | ||||||||
| Preappearance of COVID-19 | 2025 | 20 277 (22 290) |
20 487 (19 424, 21 550) |
2209 | 21 876 (30 884) |
21 439 (20 372, 22 506) |
–1598 (–3173, –23) |
–961 (–2485, 562) |
| Postappearance of COVID-19 | 785 | 19 651 (21 281) |
20 311 (18 605, 22 017) |
756 | 21 784 (26 468) |
21 719 (19 745, 23 692) |
–2133 (–4706, 440) |
–1391 (–3990, 1208) |
Abbreviations: CI, confidence interval; GLM, generalized linear model; hMPV, human metapneumovirus; N, number; RSV, respiratory syncytial virus; SD, standard deviation; US, United States.
aPopulation-averaged predictions from a GLM with a gamma distribution and log link, adjusted for age, sex, race/ethnicity, baseline healthcare utilization, kidney disease, immunocompromised status, Charlson comorbidity score, and year and month of hospitalization.
bUnadjusted mean differences are model-based contrasts from a GLM, representing the average cost difference between hMPV and RSV hospitalizations without covariate adjustment.
cAdjusted mean differences are model-based contrasts from a GLM, representing the average cost difference between hMPV and RSV hospitalizations after accounting for all covariates.
dPreappearance of COVID-19 period is defined from 1 July 2011 to 30 June 2020; postappearance of COVID-19 period is defined from 1 July 2020 to 30 June 2024.
DISCUSSION
This study indicates that hospitalization of adults with hMPV or RSV is associated with comparable and substantial healthcare costs. To our knowledge, this study is the first to describe the healthcare costs of a large cohort of adults hospitalized with laboratory-confirmed hMPV. All infections were detected by multiplex RT-PCR, which allows simultaneous detection of hMPV and RSV, among other respiratory pathogens. Therefore, testing conducted for clinical reasons, often to validate a diagnosis of influenza or SARS-CoV-2, frequently revealed hMPV or RSV infection that would have otherwise gone undetected. Respiratory pathogen testing was performed within 2 days following hospital admission among >97% of hospitalizations, reducing the likelihood that nosocomial infections impacted the analysis substantially. Furthermore, nearly 50% of tests were obtained at least 1 day after admission and test results were often not immediately available, so that initial clinical management decisions and their associated costs were unlikely to be influenced substantially by virologic diagnosis.
Despite growing evidence that hMPV and RSV infections are associated with severe illness in older adults and adults with comorbid conditions, there are limited data on the cost of hMPV-associated hospitalizations in adults. However, several studies have estimated the cost of hospitalization for RSV. A recent study estimated that RSV disease among US adults ≥60 years of age resulted in nearly 8.2 million outpatient visits, 826 790 hospitalizations, and 65 853 deaths over 5 years, resulting in nearly $3 billion in direct medical costs annually without RSV vaccination [6]. In a study spanning 15 seasons between 1997 and 2012, the cost of RSV-associated hospitalization of adults was found to be much higher than our estimate when adjusted to 2020 USD ($45 880) [7]. However, this analysis included hospitalizations prior to 2008, at which time more sensitive molecular testing for RSV became available. Therefore, their analysis may have included patients with RSV disease that was more severe than RSV disease detected by more sensitive methods in our study. Similarly, a recent study estimated the cost of hospitalization for RSV-associated lower respiratory tract infection to be $37 025 in 2023 USD, which is higher than our estimate even when adjusted to 2020 USD ($34 975) [8]. However, their estimate included claims for professional service fees that are not included in our DRG-based estimated cost. We previously found that the cost of hospitalization of older adults between 2011 and 2015 for RSV was at least as high as that for influenza ($16 034 vs $15 163, respectively, in 2013 USD), and the RSV cost adjusted for inflation ($198 71 2020 USD) [9] was similar to cost estimates in this study for hospitalization with hMPV or RSV. Although these hospitalization cost estimates may help inform cost-effectiveness analyses as vaccine and therapeutics directed against hMPV and RSV are developed, such analyses will require country-specific inputs.
The burden of disease associated with RSV and with hMPV is considerable. A landmark study of high-risk adults and adults ≥65 years of age in the United States detected RSV infection in 3%–7% of healthy community-dwelling older adults, 4%–10% of high-risk adults, and 16% of adults hospitalized with cardiopulmonary conditions [10]. In addition, RSV infection was estimated to result in ∼177 000 hospitalizations and 10 000–14 000 deaths [10]. Similarly, hMPV was estimated recently to cause over 545 000 infections and 122 000 hospitalizations among older adults in the United States, suggesting that the burden of hMPV-associated disease is comparable to that of RSV-associated disease [11, 12], although the clinical impact of hMPV and RSV may vary between seasons [13]. Severity of disease among adults hospitalized with hMPV or RSV is also similar. A recent study found that the rates of detection of hMPV and RSV among hospitalized adults ≥18 years of age in whom respiratory viruses were detected were similar (8.1% vs 9.8%, respectively). Furthermore, the LOS (4.8 vs 4.4 days) and proportion admitted to the ICU (16.5% vs 16.1%) were also comparable [14]. Likewise, a multicenter European study that compared the clinical burden of hMPV, parainfluenza virus, and RSV in hospitalized adults found that infection with RSV or hMPV results in similar hospital and ICU admission rates and morbidity and mortality among hospitalized adults [15].
Our analysis of hMPV- and RSV-associated hospitalization costs should be interpreted with caution. Since we assigned nationally representative costs to healthcare utilization, these costs may be more generalizable but may not be the actual costs for KPSC. Furthermore, NIS does not include professional fees, which may underestimate the overall healthcare cost of hospitalized adults. Additionally, the cost estimates in this study may not be generalizable to other settings and testing for hMPV and RSV was likely incomplete due to under recognition of their ability to cause serious disease. However, the comparison of the cost of hospitalization of adults with hMPV versus RSV should not be affected substantially as these limitations impact both the estimated costs of hMPV- and RSV-associated hospitalization [9]. Finally, in our results, the 95% CI of cost difference between hMPV- and RSV-associated hospitalizations crosses zero, so findings reflect no statistically significant differences rather than formal equivalence.
CONCLUSION
Both hMPV and RSV are important causes of severe illness in hospitalized adults that are associated with high hospitalization costs that are not statistically significantly different. The increasing proportion of older adults combined with the high cost of hospitalization for hMPV and RSV underscore the importance of the development of vaccines and therapeutics directed against both hMPV and RSV. Increased provider awareness of the burden and high cost of hMPV and RSV disease will be important to the utilization of these interventions when they become available.
Supplementary Material
Notes
Acknowledgments. We would like to thank the patients of Kaiser Permanente for their partnership. Their information, collected through our electronic health record system, leads to findings that help us improve care for our patients and can be shared with the larger community. An abstract covering the findings from this study has been accepted for presentation at the ESCMID Global 2026 conference.
Author contributions. All authors participated in study design, implementation, or analysis; the interpretation of the study; and/or the development of this manuscript. All authors gave final approval before submission.
Data availability. The datasets generated and/or analyzed during the current study are not publicly available to protect patient privacy.
Financial support. This work was supported by AstraZeneca.
Contributor Information
Bradley K Ackerson, Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California, USA.
Emily Rayens, Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California, USA.
Lina S Sy, Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California, USA.
Hung Fu Tseng, Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California, USA.
Lei Qian, Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California, USA.
Yi Luo, Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California, USA.
Rachelle Juan, Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California, USA.
Xuan Huang, Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California, USA.
Jennifer H Ku, Center for Integrated Health Care Research, Kaiser Permanente, Honolulu, Hawaii, USA.
Punam P Modha, Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California, USA.
Radha M Bathala, Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California, USA.
Sudhir Venkatesan, BPM Evidence Statistics, BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK.
Lisa Glasser, Vaccines and Immune Therapies, AstraZeneca, Wilmington, Delaware, USA.
Richard McNulty, Vaccines and Immune Therapies, AstraZeneca, Cambridge, UK.
Daniel Molnar, Vaccines and Immune Therapies, AstraZeneca, Barcelona, Spain.
Chengbin Wang, Vaccines and Immune Therapies, AstraZeneca, Gaithersburg, Maryland, USA.
Jaejin An, Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California, USA.
Supplementary Data
Supplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.
References
- 1. Davido B, Loubet P. The silent surge: the under-recognised burden of respiratory syncytial virus, human metapneumovirus, and parainfluenza viruses in adults. Int J Infect Dis 2025; 159:108006. [DOI] [PubMed] [Google Scholar]
- 2. Koebnick C, Langer-Gould AM, Gould MK, et al. Sociodemographic characteristics of members of a large, integrated health care system: comparison with US Census Bureau data. Perm J 2012; 16:37–41. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. O'Keeffe-Rosetti MC, Hornbrook MC, Fishman PA, et al. A standardized relative resource cost model for medical care: application to cancer control programs. J Natl Cancer Inst Monogr 2013; 2013:106–16. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Agency for Healthcare Research and Quality . Introduction to the Hcup National Inpatient Sample (NIS). 2020. Available at: https://hcup-us.ahrq.gov/db/nation/nis/NIS_Introduction_2020.jsp.
- 5. Glick HA, Doshi JA, Sonnad SS, Polsky D. Economic evaluation in clinical trials. 2nd ed. Oxford, UK: Oxford University Press, 2014. [Google Scholar]
- 6. La EM, Graham J, Singer D, et al. Cost-effectiveness of the adjuvanted RSVPreF3 vaccine among adults aged ≥60 years in the United States. Hum Vaccin Immunother 2024; 20:2432745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Pastula ST, Hackett J, Coalson J, et al. Hospitalizations for respiratory syncytial virus among adults in the United States, 1997–2012. Open Forum Infect Dis 2017; 4:ofw270. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Averin A, Atwood M, Sato R, et al. Attributable cost of adult respiratory syncytial virus illness beyond the acute phase. Open Forum Infect Dis 2024; 11:ofae097. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Ackerson B, An J, Sy LS, Solano Z, Slezak J, Tseng H-F. Cost of hospitalization associated with respiratory syncytial virus infection versus influenza infection in hospitalized older adults. J Infect Dis 2020; 222:962–6. [DOI] [PubMed] [Google Scholar]
- 10. Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med 2005; 352:1749–59. [DOI] [PubMed] [Google Scholar]
- 11. Lei J, Gillespie CW, Santoni S, Suba J, Kanesa-thasan N, Sobanjo-ter Meulen A. Incidence of human metapneumovirus among older adults in 10 high-income countries: a systematic literature review, meta-analysis, and modeling study. Open Forum Infect Dis 2025; 12:ofaf373. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Kulkarni D, Cong B, Ranjini MJK, et al. The global burden of human metapneumovirus-associated acute respiratory infections in older adults: a systematic review and meta-analysis. Lancet Healthy Longev 2025; 6:100679. [DOI] [PubMed] [Google Scholar]
- 13. Sundaram ME, McClure DL, Alonge OD, King JP, Meece JK, Nguyen HQ. Seasonal incidence of human metapneumovirus in high-risk adults with medically attended acute respiratory illness in a rural US community. Influenza Other Respir Viruses 2025; 19:e70119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Sieling WD, Goldman CR, Oberhardt M, Phillips M, Finelli L, Saiman L. Comparative incidence and burden of respiratory viruses associated with hospitalization in adults in New York city. Influenza Other Respir Viruses 2021; 15:670–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Davido B, Mamona C, Gault E, et al. “Three of a kind?” unmasking the clinical burden of human metapneumovirus and parainfluenza virus compared to respiratory syncytial virus in hospitalized adults: a pre-COVID-19 multicenter cohort study. Int J Infect Dis 2025; 164:108353. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.